rs7505

Positions:

• chr17-31317834-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014210.4(EVI2A):​c.*469C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,988 control chromosomes in the GnomAD database, including 20,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (20794 hom., cov: 32)
  • Exomes 𝑓: 0.54 (172 hom.)
• Consequence: EVI2A NM_014210.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

Genes affected

EVI2A (HGNC:3499): (ecotropic viral integration site 2A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000265118 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI2A	NM_014210.4	c.*469C>T		3_prime_UTR_variant	2/2	ENST00000462804.3	NP_055025.2
NF1	NM_001042492.3	c.4836-7986G>A		intron_variant		ENST00000358273.9	NP_001035957.1
EVI2A	NM_001003927.3	c.*469C>T		3_prime_UTR_variant	3/3		NP_001003927.1
NF1	NM_000267.3	c.4773-7986G>A		intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI2A	ENST00000462804	c.*469C>T		3_prime_UTR_variant	2/2	1	NM_014210.4	ENSP00000420557.3
NF1	ENST00000358273.9	c.4836-7986G>A		intron_variant		1	NM_001042492.3	ENSP00000351015.4
ENSG00000265118	ENST00000578584.5	c.478+474C>T		intron_variant		2		ENSP00000463981.2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76012 AN: 151788 Hom.: 20786 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.538 AC: 582 AN: 1082 Hom.: 172 Cov.: 0 AF XY: 0.534 AC XY: 314 AN XY: 588

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.688

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.501 AC: 76045 AN: 151906 Hom.: 20794 Cov.: 32 AF XY: 0.498 AC XY: 36981 AN XY: 74242

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.529

Alfa AF: 0.590 Hom.: 26834

Bravo AF: 0.478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7505; hg19: chr17-29644852;